N-(substituted-aminoethyl) 4-aminobenzoic acid diethylaminoethyl esters



Patented Dec. 23, 1952 Z,6Z3.t45

UNITED STATES PATENT OFFICE N- SUBSTITUTED-AMINOETHYL) 4 AMINO- BENZOIC ACID DIETHYLAMINOETHY L ESTERS No Drawing. Application December 8, 1949,

Serial No. 131,904

6 Claims. 1

This invention relates, in its principal aspects, to novel compounds possessing spasmolytic, histaminolytic or sympathicolytic activity. In particular it is directed to novel derivatives of the diethylamino ethanol ester of i-amino benzoic acid, and more especially to the N-substituted derivatives of the l-amino group.

It will also be understood that this invention is directed not only to these novel secondary and tertiary amines, but also to the salts thereof.

As a matter of general formulation with respect to the primary phase of this invention, the novel compounds thereof are represented by the following formula in which the symbol Et represents the ethyl radical.

\ /N. CH2. omnOo 0.01%.. calmer wherein the symbols R and R. designate alkyl, aryl alkyl and the terminal ends of a group which forms a heterocyclic structure with the nitrogen atom. Illustrative of such heterocyclic structures are the morpholino, and piperidino radicals. The symbol R. designates hydrogen, alkyl and aryl alkyl.

The following examples are members of the foregoing class of compounds and describe the methods of preparing the same.

Example 1 N- (fi-diethylamino ethyl) N- (benzyl) -4.-amino benzoic acid-B-diethylamino ethyl ester This compound has the formula:

' 17.2 grams of B-diethyl amino ethyl chloride hydrochloride and 32.6 grams of N-benzyl-iamino benzoic acid diethyl amino ethyl ester were mixed and heated in a closed vessel for 8 hours at 145-150 C. After cooling, the reaction mixture was dissolved in hot, distilled water and the cooled solution then extracted with ether. The water solution wasalkalized with sodium hydroxide solution and the free base was extracted with ether. The ether extracted was then evaporated yielding an oil, the free base, in amount of 25 grams.

The free base, the product of this example, was transformed into the oxalate salt by the addition thereto of oxalic acid in ethanol. On recrystallization from methanol plus acetone, the oxalate was obtained in a yield of 30 grams. It had a melting point of C.

Analysis calculated C30H43O10N3. 29.75%. Found: Oxalic acid 29.70%.

Example 2 N (B dimethylamino ethyl), N (benzyl) --i amino benaoic acid-,S-diethylamino ethyl ester.

This compound has the formula:

(Me)2N.Gl-12.CHz.TC o cox-murmur Example 3 Oxalic acid:

Oxalic acid:

N-(B-piperidino ethyl), -4-amino benzcie acid- B-diethylamino ethyl ester This compound has the formula:

This new product was prepared in accordance with the general procedure described in Example 1 except that fl-piperidino ethyl chloride hydrochloride was used in the place of the c-diethyl amino ethyl chloride hydrochloride of that example, and l-amino benzoic acid-B-diethyl amino ethyl ester was used in the place of the N-benzyl- 3 -amino benzoic acid fl-diethyl amino ethyl ester of that example. The oxalate salt of this new base was obtained by recrystallization from methanol in a yield of 50%. This salt had a melting point of 110 C.

Analysis: Calculated for C24H37O10N3. acid, 34.15%. Found: Oxalic acid 33.89%.

Example 4 Oxalic N- (fi-morpholino ethyl), N-.(benzyl) -4-amino benzoic acid-B-diethylamino ethyl ester This compound has the formula N.CH:.CHzNQCOOICHLCHLNUELH.

This new product was prepared-in accordance with the general procedure described in Example 1 except that fl-morpholino ethyl chloride hydrochloride was used in the place of the fi-diethyla amino ethyl chloride hydrochloride of that example.

The oxalic acid salt of this new product was obtained by recrystallization from methanol plus acetone in a yield of 55%. This salt had a meltpoint of 170 C.

Analysis Calculated. for CaoHhOnNal. acid-29.08%. Found: Oxalic-acid-29.'35%.

Emampl'e 5 Oxalic N-(p-diethyl amino ethyl-'l--amind benzoic acidec-diethylamino'ethyl ester This compoundhas the formula:

rpm. CH2. CH .TlC C o ocnrosiaxucm This new product was prepared'in accordance with the general procedure described in Example 1 except that l-amino-benzoic. acid-li-diethylamino ethyl ester was "used in the place of the N-benzyl-l-amino benzcic acid-e-diethylamino ethyl ester of that example.

The oxalic acid salt of--this new base was obtained by recrystallization .from acetone in a yield of 142? C.

Analysis: Calculated .1 for i. CzsHmGioN acid, 34.95%. Found: 341.41%.

sample 6 Oxalic N-(B-dimethylamino ethyD--amino benzoic acid-c-diethylamino ethyl ester- This compound has the formula;

amnncmcurn -o 0 com. Gamma):

This new product was prepared in accordance with thegeneral proceduredescribed irLEXample 1 except that fi-dimethylamino. ethyl chloride hydrochloride and..- 4 amino .henzoicacid-fldiethylamino ethyl ester were used in the place of the -B-diethylamino ethyl chloride hydrochlorideand the N-benzyl-4-amino benzoic acid fi-diethyl amino ethyl ester respectivelywhich were used in that example.

The oxalic acid salt of this new base'was obtained by recrystallization from methanol plus acetone inayield of 56 This salt had a'melting point of 148 C.

Analysis: Calculated for CrHasOroNx; acidy365967i: Found: Oxalic acid 36.81%.

Oxalic This salt had a 'meltingipoint of Y '4 Example 7 N (fl-piperidino ethyl), N- (benzyl) l-amino benzoic acid-p-diethylamino ethyl ester This compound has the formula:

This new product was prepared in accordance with the general procedure described in Example 1 except that 5-piperidino ethyl chloride hydrochloride was usedin the place of the B-diethylamino ethyl chloride hydrochloride of that example.

The oxalic acid'salt of this new base was obtainediby recrystallization from methanol plus acetone in a yield of 50%. This salt had a melting pointv of. 138 C;

Analysis: Calculated for C31H43O10N32 Oxalic acid, 29.17%. Found: Oxalic acid, 29.28%.

Example 8 N (eimorpholino ethyl) lamino benzoic acid-fi-diethylamino ethyl ester This compound has the formula:

(CH ll:

Analysis: Calculated for C22H34O9N3.H2O2 Oxalic acid, 26.10%. Found: Oxalic acid, 26.41%.

Example 9 N-(c-dibenzylamino' ethyl), 4-amino benzoic acid-B-diethyl amino ethyl ester This compound has the formula:

This new compound was prepared in accordance with the general procedure described in Example 1, except that the initial starting materialswere B-dibenzyl amino ethyl chloride hydrochloride and 4-amino benzoic acid-,G-diethylamino ethyl ester.

The (ii-hydrochloride salt of the new base was obtained in a yield of 40 When'recrystallizecl from ethanol'and ether, the salt had'ameltingpoint of 70 C5 Analysis Calculated for CzbHtOz'Ns'Clz: C1, 13.32%. Found:- Cl, 13.55%;

Example N- (,B-dibenzylamino ethyl) N (benzyl) -4- amino benzoic acid-fi-diethylamino ethyl ester This compound has the formula:

This new compound was prepared in accordance with the general procedure described in Example 1, except that the initial starting materials used were fi-dibenzylamino ethyl chloride hydrochloride and N-benzyl-4-amino benzoic acid-[B-diethyl amino ethyl ester.

The clihydrochloride salt of this new base was obtained in a yield of 70%. On recrystallization from ethanol and ether, this salt had a melting point of 71 C.

Analysis: calculated for C'3SH45O2N3C12! Cl, 11.39%. Found: 11.87%.

I claim:

1. Basic nitrogen compounds and their acid addition salts wherein the free base forms have the formula wherein: R and R are members of the group consisting lower alkyl, monocyclic aryl alkyl, and the terminal ends of group that forms with the nitrogen atom a ring of the group consisting of morpholino and. piperidino, and R," is a member REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,334,642 Altwegg et a1 Mar. 23, 1920 1,889,645 Eisleb Nov. 29, 1932 2,073,099 Eisleb Mar. 9, 193 2,406,627 Parker et a1 Aug. 2'7, 1946 2,456,556 Cope Dec. 14, 1948 OTHER REFERENCES Rohrmann et al.: Chem. Abstr., vol. 30, (1936), pp. 4060-4061.

Beilstein Handbuch der Org. Chemie., vol. XIV, p. 424.

Fulmer et al.: J. Am. Chem. Soc, vol. '71, pp. 1209-1210 (1949). 

1. BASIC NITROGEN COMPOUNDS AND THEIR ACID ADDITION SALTS WHEREIN THE FREE BASE FORMS HAVE THE FORMULA WHEREIN: R AND R'' ARE MEMBERS OF THE GROUP CONSISTING OF LOWER ALKYL, MONOCYCLIC ARYL ALKYL, AND THE TERMINAL ENDS OF THE GROUP THAT FORMS WITH THE NITROTEN ATOM A RING OF THE GROUP CONSISTING OF MORPHOLINO AND PIPERIDINO, AND R" IS A MEMBER OF THE GROUP CONSISTING OF HYDROGEN AND MONOCYCLIC-ARYL ALKYL. 